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Chronic lymphocytic leukemia (CLL) develops due to an imbalance between apoptosis and proliferation of B lymphocytes. Chrysin induced apoptosis in leukemia cell lines such as U937, MO7e, THP-1 and HL-60, but there has not yet been data demonstrating the apoptotic effect of chrysin on CLL cells. Therefore, in our investigation we examined the cytotoxicity of chrysin against two leukemia cell lines, MOLT-4 and JVM-13, peripheral blood lymphocytes isolated from B-CLL patients and peripheral blood mononuclear cells (PBMC) from healthy individuals in vitro. ; The effect of chrysin on viability of MOLT-4 and JVM-13 cell lines, B-CLL cells derived from 28 patients and PBMC from 16 healthy subjects was determined by MTT assay. The type of cell death induced by chrysin was verified by Annexin V/7AAD assay and acridine orange and ethidium bromide (AO/EB) staining assay. Intracellular localisation and endogenic expression of apoptotic proteins including Bax, Bcl-2, cytochrome c and caspase-3 were determined by flow cytometry and fluorescent microscopy. ; Our results demonstrated that exposure of MOLT-4, JVM-13 cell lines and B-CLL cells to the concentration of chrysin of 10?M and higher selectively decreased viability of cells in this cell population, but not in the PBMC derived from healthy subjects; LC50 values of chrysin for B-CLL cells were 51μM for 24 hours and 32μM for 48 hours of incubation, respectively. Our findings demonstrated that chrysin induces the activation of proapoptotic Bax and decreases the expression of antiapoptotic Bcl-2 protein, releases cytochrome c from mitochondria into cytosol and cleavages/activates caspase-3, subsequently leading to the activation of apoptosis of B-CLL cells. ; Together, these findings suggest that chrysin selectively induces apoptosis of peripheral blood lymphocytes isolated from human chronic lymphocytic leukemia patients via mitochondrial pathway in vitro and that it might have a promising role as a potential future antileukemic remedy.

A comprehensive understanding of the solidification process is of paramount importance for the control and prediction of actual casting characteristics. The present work presents the potential of cooling curve analysis to characterize the solidification path of a cast hypoeutectic series of Al–Si–Cu alloys. The aim of this work was to examine how variation in chemical composition of Si (from 5–9 wt.%) and Cu (from 1–4 wt.%) may affect characteristic solidification temperatures, their corresponding solid fraction, and thermal freezing ranges of the investigated alloys. All solidification parameters that have been calculated using cooling curve analysis show good correlation with the corresponding parameters calculated using commercial Pandat software. These parameters, either collected from the cooling curve analysis or calculated using Pandat software, can be easily incorporated into existing simulation software packages in order to improve their accuracy. In addition, cooling curve analysis can be used to estimate the effect of cooling rate on the above mentioned solidification parameters and used as additional input data for simulation.

Fluoroquinolones (FQLs) are synthetic antibacterial agents containing a 4-oxo-1,4-dihydroquinoline skeleton. When concomintantly administered with other drugs which may contain metal ions, particularly Al3+(antacids, phosphate binders, vaccines etc.) they may form metal–drug complexes. Pharmacokinetic studies have shown that aluminium–quinolone interactions lead to reduced bio-availability and altered activity of the drug with possible development of the toxic effects of aluminium ion. Reliable speciation in Al3+–quinolone systems at the micromolar concentration level is needed to better understand pharmaco- and toxico-kinetics of the FQLs in the presence of Al. In this work, the speciation in solutions containing Al3+and FQL family members (fleroxacin, moxifloxacin and ciprofloxacin) was studied by electrospray mass spectrometry (ESI-MS), ESI-tandem mass spectrometry and laser desorption ionisation (LDI) MS. The dominating species identified in all three Al3+–FQL solutions, at approx. 30–50 µmol L-1total Al concentration and 2:1 to 1:3 metal-to-ligand ratio in the pH range 3.0–6.0, were the ions related to the complexes AlL2+, AlL2+and AlL30(L = ligand in the mono-deprotonated form). Mixed protonated and hydroxo complexes were also formed at lower and higher pH values, respectively and, as expected, dimeric and polymeric species were not observed in ESI spectra. LDI measurements confirmed the existence of the mononuclear complexes found by ESI and indicated the formation of polymeric species. The ion [2Al3++ 5L-]+was identified with all three FQLs. This ionic species most probably arises from Al2L2by clustering with free ligand anions. Comparison of literature potentiometric data with mass spectral data indicated good agreement between speciation schemes. The results obtained suggest the presence of strong interaction between FQLs and Al3+, which may be important in affecting absorption of these drugs in the gastrointestinal tract.

The solidification path of AlSi6Cu4 alloy with various content of Sn has been investigated using cooling curve techniques. The content of Sn has been varied from 0 to 500 ppm. The hardness of as cast alloys with different content of Sn has been measured. The results show that Sn in synthetically designed AlSi6Cu4 alloy (very low level of other elements) precipitate isolated. The increased content of Sn decreases significantly the solidus temperature of this alloy, prolonging its solidification temperature interval for approximately 9K. The hardness of this alloy has been reduced for about 20% by presence of Sn up to 500 ppm.

The dendrite coherency point (DCP) temperature refers to the state of a solidifying alloy at which a coherent dendrite network is established during the formation of grains. There are three main approaches for detection of DCP: (i) the thermal analysis method, (ii) mechanical (or rheological) technique and (iii) physical method based on the thermal diffusivity measurement technique.

The impact of strontium on the solidification path of the AlSi6Cu4 aluminium alloy was examined. Strontium levels up to 210 ppm have been considered. The purpose of this study is: (i) to optimize the amount of strontium additions in AlSi6Cu4 melt in order to achieve the necessary degree of silicon modification and (ii) to observe the effects of strontium level on the other characteristic solidification temperatures of this alloy, with special emphasis on the nucleation temperature of copper rich phases. This investigation showed that a strontium level of approximately 140 ppm was sufficient to modify eutectic morphology of silicon in thermal analysis test samples. Increasing the strontium levels up to 210 ppm raises the nucleation temperature of copper rich phases, leading also to the higher area fraction of those phases.

This paper investigates the effect of some major alloying elements (silicon and copper) and the effect of grain refiner (titanium boride) on the size of the secondary dendrite arm spacing (SDAS) in series of Al-Si-Cu alloys. It has been shown that both silicon and copper have significant influence on this solidification parameter. The addition of grain refining master alloys to aluminium alloys is common practice in many commercial foundries aiming to reduce the grain size of Al-Si alloys. However, it was shown in the present paper that master alloy based on TiB had an unexpected impact on the SDAS, decreasing the size of SDAS. In addition, there is a minimum of SDAS corresponding to the presence of 0.12 wt% of titanium in Al-Si alloy. Such findings could have important implications for Al-Si alloys in particular, due to their wide spread applications in the automotive industry.

Thixomolding, as a semisolid processing approach, offers a unique opportunity to produce new Mg‐alloys by mixing different feedstock chips at room temperature. This way of blending or mixing two or more commercially available standard Mg alloys will produce a new alloy with different melting range, solidification path, phase distribution and metallurgical and mechanical properties. This paper demonstrates the applicability of thermodynamic modeling to generate detailed information about phase formation in thixomolding process. For this purpose the process is pictured by appropriate thermodynamic calculations using a multicomponent Mg alloy database.

The latent heat of solidification of any alloy depends on its chemistry that consequently affects the macro and microstructures for the given solidification conditions. In order to analyze the effects of chemistry on the release of latent heat during solidification of the industrial 3XX series of aluminum alloys, four different levels of silicon (5, 7, 9 and 11wt% Si) and three different levels of copper (1, 2 and 4 wt% of Cu) were taken into consideration. The solidification process was studied at cooling rates of 6 and 10°C/minute. The solidification path of these alloys was determined and the corresponding latent heat released during the solidification process was measured using a Differential Scanning Calorimeter (DSC). The tested hypoeutectic alloy chemical composition was expressed by the novel concept of silicon equivalency. The findings indicate that increases in the cooling rates shift the characteristic temperatures toward lower values without having a significant effect on the amount of released latent heat.

Z-Phe-Ala-glyoxal (where Z is benzyloxycarbonyl) has been synthesized and shown to be a competitive inhibitor of papain with a Ki = 3.30±0.25nM. 13C-NMR has been used to show that in aqueous media, Z-Phe-[2-13C]Ala-glyoxal gives signals at 207.7p.p.m. and 96.3p.p.m. showing that both the α-keto carbon and its hydrate are present. When this inhibitor is bound to papain a single signal at 209.7p.p.m. is observed due to the 13C-enriched carbon. This demonstrates that the glyoxal α-keto carbon is not hydrated when it is bound to papain and that it does not form a thiohemiketal with the thiol group of Cys-25. Z-Phe-[1-13C]Ala-glyoxal has also been synthesized and its aldehyde carbon is fully hydrated in aqueous solution giving signals at 88.7p.p.m. and 90.2p.p.m. when the α-keto carbon and its hydrate are present respectively. When this inhibitor is bound to papain a single signal at 71.04p.p.m. was observed due to the 13C-enriched carbon showing that the 13C-enriched aldehyde carbon forms a thiohemiacetal with Cys-25.

A new inhibitor, Z-Ala-Pro-Phe-glyoxal (where Z is benzyloxycarbonyl),has been synthesized and shown to be a competitive inhibitor of δ-chymotrypsin, with a Ki of 25±8nM at pH7.0 and 25°C. Z-Ala-Pro-[1-13C]Phe-glyoxal and Z-Ala-Pro-[2-13C]Phe-glyoxal have been synthesized, and 13C-NMR has been used to determine how they interact with δ-chymotrypsin. Using Z-Ala-Pro-[2-13C]Phe-glyoxal we have detected a signal at 100.7p.p.m. which we assign to the tetrahedral adduct formed between the hydroxy group of Ser-195 and the 13C-enriched keto-carbon of the inhibitor. This signal is in a pH-dependent slow exchange with a signal at 107.6p.p.m. which depends on a pKa of ∼ 4.5, which we assign to oxyanion formation. Thus we are the first to detect an oxyanion pKa in a reversible chymotrypsin—inhibitor complex. A smaller titration shift of 100.7p.p.m. to 103.9p.p.m. with a pKa of ∼ 5.3 is also detected due to a rapid exchange process. This pKa is also detected with the Z-Ala-Pro-[1-13C]Phe-glyoxal inhibitor and gives a larger titration shift of 91.4p.p.m. to 97.3p.p.m., which we assign to the ionization of the hydrated aldehyde hydroxy groups of the enzyme-bound inhibitor. Protonation of the oxyanion in the oxyanion hole decreases the binding efficiency of the inhibitor. From this decrease in binding efficiency we estimate that oxyanion binding in the oxyanion hole reduces the oxyanion pKa by 1.3 pKa units. We calculate that the pKas of the oxyanions of the hemiketal and hydrated aldehyde moieties of the glyoxal inhibitor are both lowered by 6.4–6.9 pKa units on binding to chymotrypsin. Therefore we conclude that oxyanion binding in the oxyanion hole has only a minor role in decreasing the oxyanion pKa. We also investigate how the inhibitor breaks down at alkaline pH, and how it breaks down at neutral pH in the presence of chymotrypsin.

The protonation and complex formation equilibria in aluminium(III) + ofloxacin (Hoflo) solutions in the presence of either cetyltrimethylammonium bromide (CTAB, 5.0 mmol L−1), cetylpyridinium chloride (CPCL, 2.0 mmol L−1) or polyethylene glycol tert-octylphenyl ether (triton X-100, 1.0 mmol L−1) have been studied by glass-electrode potentiometric measurements in a 0.1 mol L−1LiCl ionic medium at 298 K. In the concentration range 0.4 ≤ CAl≤ 1.0 mmol L−1, with a ligand to metal ratio of 1 : 1 to 5 : 1, and 3.5 ≤ −log h≤ 7.0, a non-linear least squares treatment of the data indicate that in all studied systems the complex Al(oflo)2+forms as the dominating one. Its overall stability constant (log β) is in the range 10.37–11.90 (depending on the type of surfactant), which is about 1 log unit higher than in the absence of surfactants. The formation of bis(ofloxacinato) and mixed protonated or hydrolytic complexes is largely suppressed in the presence of surfactants. The adsorption of ofloxacin on aluminium oxide was studied in neutral, acidic (0.1 mol L−1HCl) and alkaline (0.001 mol L−1NaOH) media; in absence and presence of ionic surfactants; sodium dodecylsulfate (SDS, 10 mmol L−1); or CTAB (5.0 mmol L−1). The adsorption is of the Freundlich type and is higher in neutral media with no presence of surfactants, while in an acidic medium it is significantly enhanced in the presence of SDS. Both surfactants increase the adsorption in an alkaline medium. The observed phenomena were explained based on the hydrophilic/lipophilic properties of the surfactants.

An analytical procedure for the determination of ciprofloxacin in serum without previous extraction has been developed. The determination was carried out using iron(III) nitrate as chromogenic agent, with the addition of sodium dodecylsulfate, at pH = 3.0. Absorbance was measured at 430 nm. The range of linearity was between 0.5 - 20.0 μg/mL with a detection limit 0.2 μg/mL.

The influence of strontium on the silicon modification and aluminium-copper eutectic microstructures in the 319 aluminium alloy was examined. The strontium levels considered were between 8 and 96 ppm. The purpose of this study is: (i) to observe the effects of strontium on the degree of silicon modification in the 319 aluminium alloy, and (ii) to determine the effects of strontium level on the area fraction of copper phases. The degree of silicon modification was determined using the American Foundrymen's Society (AFS) specification. The area fractions of aluminium-copper phases were examined using scanning electron microscopy (SEM) and quantitative image analysis (IA). This investigation showed that a strontium level between 75 and 85 ppm was sufficient to modify the thermal analysis test sample's silicon structure to an AFS specification No. 4. Increasing the strontium level from 8 to 96 ppm leads to the larger area fraction of the interdendritic blocky Al2Cu eutectic structure and lower area fraction of the eutectic Al-Al2Cu structure with interspersed α-Al phase in the as-cast structure.

An entire-domain method is proposed for the analysis of thin-wire antennas assembled from arbitrarily interconnected straight segments placed on one or both sides of the interface air/lossy ground. The approach is based on an exact Sommerfeld-type formulation combined with the Hallen-type integral equations for current distribution, polynomial approximation of current and point matching. Limitations on the antenna position with respect to the interface and on the value of the ground parameters seem to be less than in other available methods, and accuracy of the results depends principally on available CPU time.

The limit behaviors of three-dimensional displacements in thin linearly elastic plates, as the half-thickness ε tends to zero, is now known for various lateral boundary conditions (see [1], [5]). In the generic case one obtains that the leading term of the asymptotic series u0 + ge1+ε2u2 +… of the scaled displacement is a Kirchhoff-Love field. In this Note we investigate the case where this leading term vanishes, giving the structure of the first non-vanishing term uk and an error estimate for its deviation from the scaled solution u(ε) multiplied by ε−k. There are essentially only three new cases (uncoupling in membrane and bending). Finally, in these situations a boundary layer term of the same order as the actual leading term appears in a generic way.

The method for the direct determination of norfloxacin, without prior separation, in serum and pharmaceutical formulations, by means of fluorometry and second derivative u.v. spectrophotometry, was developed. Fluorometric assay of norfloxacin in serum was carried in 0.1 M HCl, with the adition of sodium-dodecylsulphate, at emission wavelength 450 nm (excitation 320 nm). Linear calibration curve was obtained in the concentration range 20 - 320 μg/L with the detection limit 2μg/L. The second derivative spectrophotometry was used for the determination of the norfloxacin in tablets at 337 nm using 0.05 M NaOH as solvent. Detection limit was 30μg/L.

An entire-domain method is proposed for the analysis of thin-wire antennas assembled from arbitrarily interconnected straight segments situated in imperfectly conducting layered media. Following the Sommerfeld formulation, novel recursive formulas for the Hertzian vector components for vertical and horizontal Hertzian dipole located in any layer are obtained. Such exact Sommerfeld solutions are incorporated into the Halle´n integral equations which are numerically solved by polynomial approximation of current and point matching. The Sommerfeld integral terms are evaluated numerically with high accuracy.